rs199994172

Variant names:

• chr2-127640307-G-A
• rs199994172
• NM_001161403.3:c.765C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-127640307-G-A
• chr2-127640307-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6_Very_Strong BP7

The NM_001161403.3(LIMS2):​c.765C>T​(p.Asp255Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,612,978 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000087 (0 hom.)
• Consequence: LIMS2 NM_001161403.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.632
• Publications: 1 publications found

Genes affected

LIMS2 (HGNC:16084): (LIM zinc finger domain containing 2) This gene encodes a member of a small family of focal adhesion proteins which interacts with ILK (integrin-linked kinase), a protein which effects protein-protein interactions with the extraceullar matrix. The encoded protein has five LIM domains, each domain forming two zinc fingers, which permit interactions which regulate cell shape and migration. A pseudogene of this gene is located on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

LIMS2 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy type 2W

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 2-127640307-G-A is Benign according to our data. Variant chr2-127640307-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 475550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.632 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161403.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	NM_001161403.3	MANE Select	c.765C>T	p.Asp255Asp	synonymous	Exon 8 of 10	NP_001154875.1
	LIMS2	NM_017980.5		c.837C>T	p.Asp279Asp	synonymous	Exon 8 of 10	NP_060450.2
	LIMS2	NM_001136037.4		c.831C>T	p.Asp277Asp	synonymous	Exon 9 of 11	NP_001129509.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.765C>T	p.Asp255Asp	synonymous	Exon 8 of 10	ENSP00000347240.4
	LIMS2	ENST00000324938.9	TSL:1	c.837C>T	p.Asp279Asp	synonymous	Exon 8 of 10	ENSP00000326888.5
	LIMS2	ENST00000409455.5	TSL:1	c.750C>T	p.Asp250Asp	synonymous	Exon 8 of 10	ENSP00000386383.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152178 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000284 AC: 71 AN: 249622 AF XY: 0.000318

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00305

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000869 AC: 127 AN: 1460682 Hom.: 0 Cov.: 32 AF XY: 0.0000853 AC XY: 62 AN XY: 726646

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.000246 AC: 11 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00149 AC: 59 AN: 39696

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5566

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1111926

Other (OTH) AF: 0.000133 AC: 8 AN: 60356

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152296 Hom.: 1 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.0000197 Hom.: 0

Bravo AF: 0.000162

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2W (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.1
DANN	Benign	0.83
PhyloP100		-0.63
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199994172; hg19: chr2-128397882;